Microphthalmia and cerebral atrophy induced in mouse embryos by infection with murine cytomegalovirus in midgestation.

Microphthalmia and cerebral atrophies were induced in mouse embryos after injection of murine cytomegalovirus (MCMV) into the conceptus at midgestation. The concepti of ICR mice on day 8.5 of gestation were injected with MCMV through the uterine wall, then pregnancies were allowed to continue. On day 15.5 of gestation, microphthalmia was observed in 19.2% of the MCMV-injected embryos (1 x 10(4) plaque-forming units). As the survival rate decreased when pregnancies were allowed to continue further, incidence of microphthalmia decreased, whereas cerebral atrophies, determined by examining the histological sections, were observed in 17.6% of the surviving mouse fetuses on day 18.5 of gestation. Microphthalmia was confirmed by microscopically measuring the eyes on the serial coronal sections. There were two types of microphthalmia: one with marked hypoplastic eye with periglobular mesenchymal proliferation, the other with small eye and lens without the mesenchymal proliferation. Immunohistochemical analysis was performed using antibodies specific to the nuclear antigen of MCMV. Viral antigen-positive cells were widely distributed in the mesenchymes around the oral and nasal cavities and in the mesenchymes around the brain, especially in the endothelial cells of the vessels and the perivascular mesodermal cells. In the eyes, viral antigen-positive cells were observed in mononuclear blood cells in the cavities of the vitreous bodies. These results suggest that the primary target of congenital cytomegalovirus infection may be the mesenchymal cells; then the infection extends to the eyes and brain. In addition, the mesenchymal infection may also disrupt their organogenesis, resulting in microphthalmia and cerebral atrophy. This experimental system may provide a model similar to congenital cytomegalovirus infection in humans.